This proposal describes a five year program for a clinical research based career in Infectious Diseases. The candidate, Mini Kamboj MD, an Instructor in Medicine and Associate-Director of Hospital Infection Control will conduct the program under the supervision of Dr. Kent Sepkowitz, Professor of Medicine, and Director of the Infection Control Program at Memorial Sloan-Kettering Cancer Center (MSKCC), to study the role of novel risk factors for a multi-drug resistant organism (MDRO) Vancomycin resistant enterococcus (VRE).These infections are more common in persons with cancer and result in devastating outcomes and greater resource utilization. The study will be conducted at MSKCC, one of the largest programs of clinical research in the world. The candidate has enlisted an advisory committee of esteemed leaders in the field of microbial pathogenesis, infection control and genome based testing for guidance and advice during this program. The proposal is guided by the hypothesis that many anti-cancer drugs have anti microbial properties and therefore are likely to influence gastrointestinal flora including the microbial burden (density) of VRE. We also hypothesize that a change in density of VRE in turn has an effect on clinical outcome. To examine this hypothesis we propose to (1)Determine VRE density in stool in 50 cancer patients at MSKCC using a new quantitative PCR assay and standard microbiologic techniques (2) Determine the effect of commonly used chemotherapeutic agents with strong antimicrobial activity, (5-Fluorouracil and Methotrexate) upon density of VRE among colonized individuals. (3) Determine the predictive value of VRE density determined by standard techniques and quantitative PCR on clinical outcome, including mortality and resource utilization, among patients with cancer at highest risk for invasive VRE disease. The candidate's immediate goal is to develop into an independent clinical investigator in patient-oriented clinical research with a focus on hospital acquired infections in persons with cancer and long term goal is to implement studies on devising and testing therapeutic approaches including decolonizing and other control strategies for MDRO's that are common in the cancer population. Hospital-acquired infections are a major cause of morbidity and mortality in persons with cancer. In this population, colonization and infection with vancomycin-resistant enterococci are more common. The studies in this proposal will provide novel insight into common but previously unrecognized risk factors for VRE in persons with cancer and provide a basis for devising and testing control strategies against this multi-drug resistant organism.